{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:47:32Z","timestamp":1792194452242,"version":"4.4.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2012,7,26]],"date-time":"2012-07-26T00:00:00Z","timestamp":1343260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by osteopenia and easy susceptibility to fracture. Symptoms are most prominent during childhood. Although antiresorptive bisphosphonates have been widely used to treat pediatric OI, controlled trials show improved vertebral parameters but equivocal effects on long-bone fracture rates. New treatments for OI are needed to increase bone mass throughout the skeleton. Sclerostin antibody (Scl-Ab) therapy is potently anabolic in the skeleton by stimulating osteoblasts via the canonical wnt signaling pathway, and may be beneficial for treating OI. In this study, Scl-Ab therapy was investigated in mice heterozygous for a typical OI-causing Gly\u2192Cys substitution in col1a1. Two weeks of Scl-Ab successfully stimulated osteoblast bone formation in a knock-in model for moderately severe OI (Brtl\/+) and in WT mice, leading to improved bone mass and reduced long-bone fragility. Image-guided nanoindentation revealed no alteration in local tissue mineralization dynamics with Scl-Ab. These results contrast with previous findings of antiresorptive efficacy in OI both in mechanism and potency of effects on fragility. In conclusion, short-term Scl-Ab was successfully anabolic in osteoblasts harboring a typical OI-causing collagen mutation and represents a potential new therapy to improve bone mass and reduce fractures in pediatric OI. \u00a9 2013 American Society for Bone and Mineral Research<\/jats:p>","DOI":"10.1002\/jbmr.1717","type":"journal-article","created":{"date-parts":[[2012,7,27]],"date-time":"2012-07-27T01:01:53Z","timestamp":1343350913000},"page":"73-80","source":"Crossref","is-referenced-by-count":119,"title":["Sclerostin antibody improves skeletal parameters in a Brtl\/+ mouse model of osteogenesis imperfecta"],"prefix":"10.1093","volume":"28","author":[{"given":"Benjamin P","family":"Sinder","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA"},{"name":"Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M","family":"Eddy","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S","family":"Ominsky","sequence":"additional","affiliation":[{"name":"Department of Metabolic Disorders, Amgen, Inc., Thousand Oaks, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle S","family":"Caird","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan C","family":"Marini","sequence":"additional","affiliation":[{"name":"Bone and Extracellular Matrix Branch, National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth M","family":"Kozloff","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA"},{"name":"Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,7,26]]},"reference":[{"key":"2024020318451619600_bib1","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nrendo.2011.81","article-title":"New perspectives on osteogenesis imperfecta","volume":"7","author":"Forlino","year":"2011","journal-title":"Nat Rev Endocrinol"},{"key":"2024020318451619600_bib2","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/S0140-6736(04)16101-1","article-title":"Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year randomised placebo-controlled study","volume":"363","author":"Sakkers","year":"2004","journal-title":"Lancet"},{"key":"2024020318451619600_bib3","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1359\/JBMR.041232","article-title":"Intravenous neridronate in children with osteogenesis imperfecta: a randomized controlled study","volume":"20","author":"Gatti","year":"2005","journal-title":"J Bone Miner Res"},{"key":"2024020318451619600_bib4","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1359\/JBMR.050109","article-title":"Controlled trial of pamidronate in children with types III and IV osteogenesis imperfecta confirms vertebral gains but not short-term functional improvement","volume":"20","author":"Letocha","year":"2005","journal-title":"J Bone Miner Res"},{"key":"2024020318451619600_bib5","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1359\/jbmr.090213","article-title":"Risedronate in the treatment of mild pediatric osteogenesis imperfecta: a randomized placebo-controlled study","volume":"24","author":"Rauch","year":"2009","journal-title":"J Bone Miner Res"},{"key":"2024020318451619600_bib6","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1210\/jc.2010-0636","article-title":"Alendronate for the treatment of pediatric osteogenesis imperfecta: a randomized placebo-controlled study","volume":"96","author":"Ward","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"2024020318451619600_bib7","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1359\/jbmr.080511","article-title":"Bisphosphonate-induced osteopetrosis: novel bone modeling defects, metaphyseal osteopenia, and osteosclerosis fractures after drug exposure ceases","volume":"23","author":"Whyte","year":"2008","journal-title":"J Bone Miner Res"},{"key":"2024020318451619600_bib8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/jbmr.173","article-title":"Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody","volume":"26","author":"Padhi","year":"2011","journal-title":"J Bone Miner Res"},{"key":"2024020318451619600_bib9","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1096\/fj.05-4221fje","article-title":"Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation","volume":"19","author":"Poole","year":"2005","journal-title":"FASEB.J"},{"key":"2024020318451619600_bib10","doi-asserted-by":"crossref","first-page":"19883","DOI":"10.1074\/jbc.M413274200","article-title":"Sclerostin binds to LRP5\/6 and antagonizes canonical Wnt signaling","volume":"280","author":"Li","year":"2005","journal-title":"J Biol Chem"},{"key":"2024020318451619600_bib11","doi-asserted-by":"crossref","first-page":"19489","DOI":"10.1074\/jbc.M110.190330","article-title":"Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function","volume":"286","author":"Leupin","year":"2011","journal-title":"J Biol Chem"},{"key":"2024020318451619600_bib12","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1359\/jbmr.081206","article-title":"Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis","volume":"24","author":"Li","year":"2009","journal-title":"J Bone Miner Res"},{"key":"2024020318451619600_bib13","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1002\/jbmr.14","article-title":"Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength","volume":"25","author":"Ominsky","year":"2010","journal-title":"J Bone Miner Res"},{"key":"2024020318451619600_bib14","doi-asserted-by":"crossref","first-page":"37923","DOI":"10.1074\/jbc.274.53.37923","article-title":"Use of the Cre\/lox recombination system to develop a non-lethal knock-in murine model for osteogenesis imperfecta with an \u03b11(I) G349C substitution","volume":"274","author":"Forlino","year":"1999","journal-title":"J Biol Chem"},{"key":"2024020318451619600_bib15","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1359\/JBMR.040111","article-title":"Brittle IV mouse model for osteogenesis imperfecta IV demonstrates postpubertal adaptations to improve whole bone strength","volume":"19","author":"Kozloff","year":"2004","journal-title":"J Bone Miner Res"},{"key":"2024020318451619600_bib16","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1359\/jbmr.080804","article-title":"Cellular mechanism of decreased bone in Brtl mouse model of OI: imbalance of decreased osteoblast function and increased osteoclasts and their precursors","volume":"23","author":"Uveges","year":"2008","journal-title":"J Bone Miner Res"},{"key":"2024020318451619600_bib17","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/j.bone.2009.07.078","article-title":"Beam hardening artifacts in micro-computed tomography scanning can be reduced by X-ray beam filtration and the resulting images can be used to accurately measure BMD","volume":"45","author":"Meganck","year":"2009","journal-title":"Bone"},{"key":"2024020318451619600_bib18","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1109\/TSMC.1979.4310076","article-title":"A threshold selection method from gray-level histograms","volume":"9","author":"Otsu","year":"1979","journal-title":"IEEE Trans Syst Man Cybern"},{"key":"2024020318451619600_bib19","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1046\/j.1365-2818.1997.1340694.x","article-title":"A new method for the model-independent assessment of thickness in three-dimensional images","volume":"185","author":"Hildebrand","year":"1997","journal-title":"J Microsc"},{"key":"2024020318451619600_bib20","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1557\/JMR.1992.1564","article-title":"An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments","volume":"7","author":"Oliver","year":"1992","journal-title":"J Mater Res"},{"key":"2024020318451619600_bib21","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/jbmr.5650020617","article-title":"Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee","volume":"2","author":"Parfitt","year":"1987","journal-title":"J Bone Miner Res"},{"key":"2024020318451619600_bib22","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1007\/s00223-005-0148-y","article-title":"Rapid establishment of chemical and mechanical properties during lamellar bone formation","volume":"77","author":"Busa","year":"2005","journal-title":"Calcif Tissue Int"},{"key":"2024020318451619600_bib23","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1002\/jbm.a.32442","article-title":"van der Meulen MCH. Effects of tissue age on bone tissue material composition and nanomechanical properties in the rat cortex","volume":"92","author":"Donnelly","year":"2010","journal-title":"J Biomed Mater Res A"},{"key":"2024020318451619600_bib24","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1080\/01926230252929882","article-title":"Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1-34) for 2 years and relevance to human safety","volume":"30","author":"Vahle","year":"2002","journal-title":"Toxicol Pathol"},{"key":"2024020318451619600_bib25","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1359\/jbmr.2003.18.2.237","article-title":"Positive linear growth and bone responses to growth hormone treatment in children with types III and IV osteogenesis imperfecta: high predictive value of the carboxyterminal propeptide of type I procollagen","volume":"18","author":"Marini","year":"2003","journal-title":"J Bone Miner Res"},{"key":"2024020318451619600_bib26","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1056\/NEJMc062792","article-title":"Prolonged bisphosphonate release after treatment in children","volume":"356","author":"Papapoulos","year":"2007","journal-title":"N Engl J Med"},{"issue":"6","key":"2024020318451619600_bib27","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1359\/JBMR.040126","article-title":"Suppressed bone turnover by long-term bisphosphonate treatment accumulates microdamage but maintains intrinsic material properties in cortical bone of dog rib","volume":"19","author":"Komatsubara","year":"2004","journal-title":"J Bone Miner Res"},{"key":"2024020318451619600_bib28","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s002230010036","article-title":"Bisphosphonate treatment suppresses not only stochastic remodeling but also the targeted repair of microdamage","volume":"69","author":"Li","year":"2001","journal-title":"Calcif Tissue Int"},{"key":"2024020318451619600_bib29","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1359\/jbmr.2000.15.4.613","article-title":"Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib","volume":"15","author":"Mashiba","year":"2000","journal-title":"J Bone Miner Res"},{"key":"2024020318451619600_bib30","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/S8756-3282(01)00414-8","article-title":"Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles","volume":"28","author":"Mashiba","year":"2001","journal-title":"Bone"},{"key":"2024020318451619600_bib31","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1007\/s00223-008-9131-8","article-title":"Alendronate reduces bone toughness of ribs without significantly increasing microdamage accumulation in dogs following 3 years of daily treatment","volume":"82","author":"Allen","year":"2008","journal-title":"Calcif Tissue Int"},{"key":"2024020318451619600_bib32","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.bone.2011.12.007","article-title":"Increased susceptibility to microdamage in Brtl\/+ mouse model for osteogenesis imperfecta","volume":"50","author":"Davis","year":"2012","journal-title":"Bone"},{"key":"2024020318451619600_bib33","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1359\/jbmr.081238","article-title":"Alendronate treatment of the Brtl osteogenesis imperfecta mouse improves femoral geometry and load response before fracture but decreases predicted material properties and has detrimental effects on osteoblasts and bone formation","volume":"24","author":"Uveges","year":"2009","journal-title":"J Bone Miner Res"},{"key":"2024020318451619600_bib34","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.matbio.2007.06.005","article-title":"Selective retention and degradation of molecules with a single mutant [alpha]1(I) chain in the Brtl IV mouse model of OI","volume":"26","author":"Forlino","year":"2007","journal-title":"Matrix Biol"},{"issue":"Suppl 1)","key":"2024020318451619600_bib35","article-title":"Altered transcript pattern during osteoblast differentiation associated with improved bone phenotype in homozygous osteogenesis imperfecta Brtl mice","volume":"26","author":"Reich","year":"2011","journal-title":"J Bone Miner Res"},{"key":"2024020318451619600_bib36","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1002\/art.30385","article-title":"Sclerostin antibody treatment enhances bone strength but does not prevent growth retardation in young mice treated with dexamethasone","volume":"63","author":"Marenzana","year":"2011","journal-title":"Arthritis Rheum"},{"key":"2024020318451619600_bib37","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1359\/jbmr.080216","article-title":"Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength","volume":"23","author":"Li","year":"2008","journal-title":"J Bone Miner Res"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.1717","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/28\/1\/73\/56563998\/1717_ftp.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/28\/1\/73\/56563998\/1717_ftp.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T10:47:33Z","timestamp":1710326853000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/28\/1\/73-80\/7598737"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7,26]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2012,7,26]]},"published-print":{"date-parts":[[2013,1,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.1717","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.720910253.793509202","asserted-by":"object"}]},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,1,1]]},"published":{"date-parts":[[2012,7,26]]}}}